The gut's feeling on bile acid signaling in NAFLD

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The gut to live axis plays a critical role in regulation of hepatic bile acid synthesis and metabolic homeostasis (1). Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with a high prevalence of~35% in adults. NAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. NAFLD is associated with insulin resistance, obesity and type 2 diabetes. Bile acid-activated fesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (Gpbar-1, aka TGR5) have been shown to regulate lipid, glucose and energy metabolism and activation of FXR by agonists have been shown to improve hepatic metabolism and metabolic disorder in several mouse models of NASH (2). However, the role of bile acid signaling in pathogenesis and treatment of NASH is not clear.
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